Companies have tried for decades to deliver protein-based drugs orally. Can Mir Imran and his company’s robotic pill succeed where so many have failed?

Mir Imran has been building medical device companies for 40 years. Perhaps known best for his work on the first FDA-approved implantable cardioverter defibrillator, Imran’s model is to identify big, unsolved challenges and try to find solutions.

His work at Rani Therapeutics, developing an oral drug-delivery capsule to replace painful injections, is no exception. Administering biologics orally has been attempted by 100 different people over the last fifty years, with no success, according to Imran.

“It’s such a compelling problem from a patient comfort and patient compliance standpoint. For companies, it could be a strategic, competitive edge over their competitors who are delivering drugs by injection,” he told Drug Delivery Business News.

Rani Therapeutics’ investigational capsule is designed to survive the human stomach’s harsh environment thanks to a polymer coating. When it arrives in the intestine, the coating dissolves and triggers a series of reactions that transforms the capsule into an auto-injector, delivering the drug directly to the intestinal wall.

“The biggest unknown right now is how well it will work in humans,” Imran said.

Developing the “robotic pill”

Imran and his team have been working on the Rani Pill for the last six years, fine-tuning the chemical reactions that power the device. The company’s capsule is often described as a robot, because it appears to have a mind of its own, Imran said.

Early on, the company decided that if they were going to inject a drug into the intestinal wall, they couldn’t use metal needles. Instead, they loaded a dissolvable polymer with a dry-powder drug and made needles out of it.

From there, the team had to figure out how the capsule would push the needles into a person’s intestinal wall. To resolve that challenge, Rani Therapeutics used a chemical reaction that produces carbon dioxide to inflate a small balloon. The balloon pushes the dissolvable needles into the intestinal wall in a process that Imran describes as “painless.”

Imran’s technology has received a great deal of interest from investors and pharmaceutical companies. Rani Therapeutics raised $53 million in February this year from companies like AstraZeneca, Novartis, Shire and Alphabet’s Google Ventures.

Beyond the financial support, Rani Therapeutics has also inked strategic partnerships with the three aforementioned pharmaceutical companies. Most recently, it agreed to an exclusive deal with Shire to combine the Rani Pill with Shire’s factor VIII therapy for patients with hemophilia A.

“We’re converting an intravenous drug to an oral, which is a huge leap,” Imran said.

He added that Rani Therapeutics has fielded interest from a number of other companies, but that he has chosen partners strategically.

“In the future we might be adding more partners, but we’re a small company so we want to make sure we do a good job for all of our partners. In a number of cases, we’ve said no mainly because of our bandwidth limitation,” he explained.

Tackling impossible problems

Throughout Imran’s lengthy career in medtech, he has learned valuable lessons about innovating around previously-unsolved challenges.

“You have to pick the right problem,” he said. “One of the challenges here is when you are doing something that is disruptive, that has never been done before, there is risk. Even for us, there is a lot of risk that we could fail at it. It’s generally easier to develop technologies that are instrumental innovations to existing technologies.”

With the biologics market pegged to be worth nearly $400 billion by 2025, according to Grand View Research, companies are desperate for better ways to deliver these protein-based medicines. Biologics are traditionally administered via injection, since they aren’t ideal for oral delivery; enzymes and the acidic environment of the stomach chew up biologic drugs before they can be absorbed.

“Lot of companies fail because they are tackling the impossible problems,” Imran said.

Looking ahead, this medtech veteran is also hoping to solve other challenging drug-delivery problems, like getting medicines past the blood-brain barrier. In the meantime, Rani Therapeutics plans to automate and scale up its manufacturing process in preparation for first-in-man studies of the Rani Pill within the next year.

“Very few drug-delivery platforms will have such a profound impact on so many chronic diseases. I’m trying to get that message across because this could be a huge benefit to the patients, to the payers and for the doctors who are treating these patients,” Imran said.

Comments

The financial problem for the patient on Medicare with oral drugs is that they are covered under Part D, which means that the patient, for expensive drugs, must pay an annual deductable of over $3,000, and then 10% of the cost of the drug for the year. For, say, a drug costing $100,000 per year, this results in another $10,000 dollars paid by the patient. If the drug is injected or infused at a hospital, there is no charge to the patient. If given a choice of an expensive drug as a pill or an injection/infusion in a hospital, for financial reasons, I opt for the injection/infusion. The irony is that an oral biologic will INCREASE the cost to the patient, no doubt leading to inferior medical care as patients either cannot afford to pay the deductables or opt to skip some, of the combination therapy drugs.